A universal feature of fertilization in mammals is that the fertilizing sperm evokes a series of repetitive calcium oscillations in the egg that persist for several hours and terminate with pronucleus formation. This pattern of calcium oscillations in mice is essential for both early events of egg activation in response to fertilization and for full term intrauterine development to occur. The factor within sperm responsible for inducing these calcium oscillations is a testis-specific phospholipase C, PLC zeta, which is released from the sperm head after sperm-egg plasma membrane fusion, and is found in all mammalian sperm studied to date, including human. Calcium oscillations are also controlled by factors within the egg. Studies are being performed using the mouse model to examine molecules within the egg that are responsible for controlling calcium oscillation behavior and calcium reuptake, processes that are essential for the continuation of calcium oscillations at fertilization. We found that during maturation, eggs take up calcium via low voltage, T-type calcium channels and that this calcium uptake regulates the calcium oscillatory pattern observed at fertilization. Additional studies using mice lacking STIM1 and all seven TRPC channels demonstrated that none of these proteins are required for normal calcium oscillations. We are in the process of deleting phospholipase C beta 1 from mouse eggs using a conditional mouse knockout strategy to determine if the egg protein is needed for production of normal calcium oscillations. We anticipate that by achieving a better understanding of the molecular and cellular modes of regulation of calcium oscillatory behavior during egg activation, we can learn how early embryo development is altered by environmental factors and by disease states. A number of essential molecules are encoded by maternal mRNAs that are dormant until oocyte maturation. One of these molecules, MED13, is a component of the Mediator complex that interacts with RNA polymerase to regulate transcription. We are currently examining the function of MED13 in programming gene expression during early preimplantation embryo development. These studies will shed light on basic genetic processes that can be disrupted by exposure to environmental chemicals and could impact on human fertility.